Rapidly disintegrating or dissolving pharmaceutical dosage forms are available for human patients who have difficulty swallowing conventional tablets or capsules, and for the sublingual and buccal administration of drugs.
Freeze-dried or lyophilized dosage forms are generally known to rapidly dissolve or disintegrate in the mouth. These forms consist of a porous matrix of a water-soluble or water-dispersible carrier material which is impregnated with a unit dose of the pharmaceutical active. These dosage forms are prepared by first adding the pharmaceutical active to a solution comprising the carrier material and a suitable solvent, typically water. The resulting composition is then subjected to a freeze drying procedure whereby the solvent sublimes under a high vacuum.
While freeze-dried dosage forms dissolve rapidly, they must be manufactured on expensive lyophilization equipment. Further, these dosage forms have generally only been used with water-insoluble actives that are relatively tasteless, because they disintegrate in the mouth, rather than being swallowed as in the case of conventional tablets and capsules.
Water-soluble drugs are generally avoided in freeze-dried dosage forms because of the dissolution of the drug in the mouth, which results in a bitter or otherwise objectionable taste. Further problems can arise when water-soluble drugs are used because of the formation of eutectic mixtures, which lower the freezing point of the formulation, resulting in incomplete freezing or melting during the freeze-drying process. This phenomenon results in product loss.
M. S. Amer in U.S. Pat. No. 4,866,046, issued Sep. 12, 1989, describes an aspirin tablet that rapidly dissolves in the oral, preferably sublingual, cavity within 2-60 seconds. This tablet provides rapid absorption of aspirin from the saliva into the blood stream. The sublingual tablet is prepared by compressing into slugs a mixture of starch (10% moisture), acetylsalicylic acid, flavor and sweetener. The slugs are then ground (14-16 Mesh size) and recompressed into tablets. An amino acid may also be used with the aspirin for its solubilizing and a taste-neutralizing effects.
U.S. Pat. No. 5,082,667, issued Jan. 21, 1992, to K. G. Van Scoik discusses a tablet triturate dosage that quickly dissolves quickly in the buccal cavity. The form includes a porous, cementatory network of a water-soluble but ethanol-insoluble carbohydrate, which contains discrete particles of the active ingredient that have been coated with a triglyceride coating. The discrete particles are prepared by suspending the active ingredient in molten triglyceride. The discrete particles are mixed with the carbohydrate and a temporary liquid binder to form a damp mass. The mass is then shaped into a tablet and dried to form the tablet triturate.
The tablet triturate of Van Scoik is limited to active ingredients, such estazolam, that are not sensitive to the melting temperature of the triglyceride. Further, since the dosage form is formed into a damp mass and subsequently dried, conventional, compression tableting machines cannot be used to manufacture this product.
J. A. McCarty, in U.S. Pat. No. 5,112,616, issued May 12, 1992, discusses a fast dissolving buccal tablet containing a buccally absorbable active ingredient, a pharmaceutically acceptable lubricant and a soluble, directly compressible tablet excipient, such as sucrose or lactose. These ingredients are mixed together and compressed into the final tablet form. Since the active ingredient is not coated, patient compliance, especially in children, would be an issue if the pharmaceutical had a bitter or otherwise objectional taste.
A need, therefore, exists for a rapidly disintegrating dosage form containing taste-masked pharmaceutical particles that can be manufactured without the use of water or solvents, and compressed on conventional tableting machines. This dosage form should be suitable for use with both water-soluble and water-insoluble actives which may have an objectional taste.